Ellestad et al, J. Med. Chem. 41, 2671 (1998) and U.S. Pat. No. 5,852,015 describe a method for preparation and purification of 4′,4-bis-{4,6-bis-[3-(bis-carbamoyl-methyl-1-sulfamoyl)-phenylamino]-[1,3,5]triazin-2-ylamino}-biphenyl-2,2′-disulfonic acid. The intermediates of this disclosed process, when used in subsequent steps lead to an approximately 70% product purity by HPLC, which requires extensive reverse phase chromatographies, followed by lyophilization to remove residual solvents. The process of Ellestad et al. may be summarized in the following Scheme I. 
The use of pure intermediates leads to a higher purity crude 4′,4-bis-{4,6-bis-[3-(bis-carbamoyl-methyl-1-sulfamoyl)-phenylamino]-[1,3,5]triazin-2-ylamino}-biphenyl-2,2′-disulfonic acid. Formation of impurities that require chromatography to remove can be further reduced by performing the last reaction step at a temperature range of 60-75° C. A purity of better than 80% can be obtained. It is desirable to have a process by which even greater purity can be achieved.